SUMMARY: In the study proposed here we will analyze the biochemistry and function of myocardial hypertrophy in the isolated perfused heart. In addition, liposomes will be used to transport trapped "in vivo - hypertrophying factors," such as norepinephrine and thyroxine, into the myocardial muscle fiber to assess differences between intracellular transport of inciting factors of cardiac hypertrophy relative to administering these factors in the free form to the isolated heart. Some of the cellular analyses made to assess hypertrophy will be synthesis and turnover of myofibrillar proteins, mainly myosin subunits, troponin, tropomyosin, and actin; other analyses will be made such as degree of protein degradation, phosphorylation of myosin, increased synthesis of total myosin light chains, and synthesis of myosin isozymes. Using the perfused isolated heart, we can obtain highly labeled myosin and thus determine if the myosin synthesized under hypertrophying conditions is a new or modified type of myosin, as has been proposed. Besides biochemical analyses, physiological changes of the heart will be monitored. The effects of such factors as increased workload, increased barometric pressure, temperature, and the presence of such factors as norepinephrine and thyroxine, shuttled into the cell via liposomal transport, will be studied relative to effects on cardiac hypertrophy. We can assess whether pressure overload induced by an increased workload, or whether an increased barometric pressure placed directly on the whole heart can also act as an inciting stimulus for cardiac hypertrophy. Such studies as designed here should provide a better insight into understanding the stimuli of hypertrophy, and to help determine whether all hypertrophy, independent of the stimulus, have a common denominator, such as increased workload leading to the stretching of the fiber vs as increased barometric pressure placed directly on the entire heart; also we will determine whether all hypertrophy independent of the origin, may be induced by a decrease of high energy compounds, and thus effect protein synthesis in this manner. In the studies designed here we hope to gain an insight into the differences between pathological and physiological hypertrophy, ascertaining how protein degradation and availability of high energy phosphate compounds may be more prevalent in one type of hypertrophy as compared to the other.